Medical Design Briefs - August 2023 - 8

Implantable Drug-Delivery Systems
a drug-eluting component will take, and what the processing
temperatures are for a chosen excipient polymer.
Ideal Drug-Delivery Window. Polymer excipient materials in
use today can be classified as either biodurable or biodegradable
and the ideal drug-delivery window will determine which
type is best for the product.
Biodurable materials are inert and do not pose any threat to
the patient. However, they do not break down in the body, so
they are best suited for long-term drug-delivery applications.
The most commonly used biodurable materials are:
* Silicone.
* Ethylene-vinyl acetate (EVA).
* Thermoplastic polyurethanes (TPU).
Biodegradable polymers do break down in the body so
a follow- up procedure to retrieve an exhausted drug core is
unnecessary. However, because the polymer breaks down over
time, it limits the life of an implant to less than six months.
Examples of biodegradable polymers are:
* Polylactic acid (PLA).
* Polyglycolic acid (PGA).
* A combination of PLA and PGA to create PLGA.
* Polyethylene glycol (PEG).
Design of the Drug-Eluting Component. The form of a
drug-delivery component may also influence the choice of excipient
material. Typically, if there are no requirements for the
excipient material other than to carry the drug and provide a
predictable dose to the patient, the simplest designs are rod,
sleeve, or ring shapes. These designs allow for the greatest flexibility
to mold or extrude products efficiently.
However, if the design is inorganic and needs to affix to
other components in an assembly, or if it needs to be a certain
shape to hold its place in the body, the product may
need to be custom molded. In these cases, the manufacturing
method for the component will dictate the excipient materials,
which will impact the elution rate of the drug from a
delivery system. For example, drugs elute out of heat-cured
rubber (HCR) silicone systems more slowly than out of a liquid
silicone rubber. These differences must be considered
and evaluated to have success in the development of a product
concept.
Required Processing Temperatures. Lastly, there must be
a comparison of the desired excipient polymer's processing
temperatures and a drug's melting point. Some compounds
do not have the ability to stand up to the temperatures required
to cure or form some of the excipient polymers. In
the early design stages, this guides therapy developers to select
one or several polymer candidates that can be cured at
temperatures and allow the drug to remain stable. However,
different formulation methods can also allow for the introduction
of a drug after forming the polymeric component,
making processing temperatures a nonissue.
Formulation
There are several methods that can be used to combine
the drug and polymer together. Beyond how to produce
the excipient polymer in its final form, therapy developers
may also consider when it is best to introduce the drug
into the system. As mentioned, drug compounds with
low melting points may break down if exposed to certain
temperatures during the manufacturing process, and the
8
chemistry of the drug may inhibit the curing or forming
process of some polymers. In these situations, it may be
important to investigate different formulation methods to
find solutions.
* Mix and Manufacture - The most used process is where both
the drug compound and excipient materials are mixed prior
to the manufacturing process. This approach typically allows
for the most efficiency but is more likely to encounter the
heat sensitivity and obstruction of cure challenges.
* Immerse and Impregnate - The introduction of the drug
to the system after completion of the manufacturing process
can allow for successful introduction of the drug while
avoiding the heat-intensive steps involved in most manufacturing
processes. It is a viable alternative for a drug with
heat sensitivities but may also limit the drug loading within
the system.
* Membrane Application - Used in situations where a drug
in a solid or crystalline state can be effectively enclosed behind
a membrane. This same approach can also be applied
to slow the release rate to a desired profile. The downside
to consider here is that a membrane is typically an additional
component within an assembly that may limit process
efficiencies.
Downstream Considerations
Therapy producers should keep in mind what happens after
the realization of a product concept. It can be easy to overlook
other processes required to bring a product to market. The following
areas can be obstacles that should be considered early
in development:
* Test method identification and development.
* Identification and testing for critical-to-quality characteristics
of a product.
* Inspection systems to identify product failures.
* Product assembly and packaging.
* Scaling for desired product quantities.
* Sterilization needs and methods.
Conclusion
With all the benefits implantable systems offer therapy developers,
clinicians, and patients it is easy to see why market
projections for this segment are on the rise. Device manufacturers
will continue to develop novel solutions that will result in
higher quality, safer treatments that improve patient outcomes.
However, the manufacturing decisions that go into creating
these systems require an experienced partner that can help
therapy developers quickly identify solutions and develop formulation
methods for use in applications.
References
1. " Global $29.84 Billion Implantable Drug Delivery Devices Markets, 2015-2020,
2020-2025F, " Research and Markets, August 2021, https://www.globenews
wire.com/en/news-release/2021/08/12/2279463/28124/en/Global-29-84Billion-Implantable-Drug-Delivery-Devices-Markets-2015-2020-2020-2025F.
html
This
article was written by Zach Fletcher, Business Development
Manager, Implantable Drug Delivery & Combination Devices,
Trelleborg Healthcare & Medical, Fort Wayne, IN. For
more information, contact Zach.Fletcher@trelleborg.com or
visit www.trelleborg.com.
www.medicaldesignbriefs.com
Medical Design Briefs, August 2023

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Medical Design Briefs - August 2023

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